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Junior Wells was possibly born in Memphis, Tennessee, United States,[1] and raised in West Memphis, Arkansas, though other sources report that his birth was in West Memphis, Arkansas.[2] Initially taught by his cousin, Junior Parker, and Sonny Boy Williamson II, Wells learned how to play the harmonica by the age of seven with surprising skill. He moved to Chicago in 1948 with his mother after her divorce and began sitting in with local musicians at house parties and taverns.[3] Wild and rebellious but needing an outlet for his talents, he began performing with The Aces (guitarist brothers Dave and Louis Myers and drummer Fred Below) and developed a more modern amplified harmonica style influenced by Little Walter.[3] In 1952, he made his first recordings, when he replaced Little Walter in Muddy Waters' band and appeared on one of Muddy's sessions for Chess Records in 1952.[3] His first recordings as a band leader were made in the following year for States Records.[4] In the later 1950s and early 1960s, he also recorded singles for Chief Records and its Profile Records subsidiary, including "Messin' with the Kid", "Come on in This House", and "It Hurts Me Too", which would remain in his repertoire throughout his career. His 1960 Profile single "Little by Little" (written by Chief owner and producer Mel London) reached #23 in the Billboard R&B chart, making it the first of two Wells' singles to enter the chart.[5]

From Wells' "Hoodoo Man Blues" album cover Junior gives this story: "I went to this pawnshop downtown and the man had a harmonica prices at $2.00. I got a job on a soda truck... played hookey from school ... worked all week and on Saturday the man gave me a dollar and a half. A dollar and a half! For a whole week of work. I went to the pawnshop and the man said the price was two dollars. I told him I had to have that harp. He walked away from the counter – left the harp there. So I laid my dollar-and-a-half on the counter and picked up the harp. When my trial came up, the judge asked my why I did it. I told him I had to have that harp. The judge asked me to play it and when I did he gave the man the 50 cents and hollered "Case dismissed!" (1948)

Wells began to have serious health problems, including cancer and a heart attack, in 1997.[3] He died in Chicago on January 15, 1998, and was interred in the Oak Woods Cemetery, Chicago.[1][7]

Wells was mentioned in the Steppenwolf song, "Tighten Up Your Wig", in which the lyrics explicitly state that they copied the music from Junior Wells' tune, "Messing with the Kid".